title: Endogenous zinc depresses GABAergic transmission via T-type Ca(2+) channels and broadens the time window for integration of glutamatergic inputs in dentate granule cells.
abstract: Zinc actions on synaptic transmission span the modulation of neurotransmitter receptors, transporters, activation of intracellular cascades and alterations in gene expression. Whether and how zinc affects inhibitory synaptic signalling in the dentate gyrus remains largely unexplored. We found that mono- and di-synaptic GABAergic inputs onto dentate granule cells were reversibly depressed by exogenous zinc application and enhanced by zinc chelation. Blocking T-type Ca(2+) channels prevented the effect of zinc chelation. When recording from dentate fast-spiking interneurones, zinc chelation facilitated T-type Ca(2+) currents, increased action potential half-width and decreased spike threshold. It also increased the offset of the input-output relation in a manner consistent with enhanced excitability. In granule cells, chelation of zinc reduced the time window for the integration of glutamatergic inputs originating from perforant path synapses, resulting in reduced spike transfer. Thus, zinc-mediated modulation of dentate interneurone excitability and GABA release regulates information flow to local targets and hippocampal networks.
authors.affiliation: A. J. Ruiz: Department of Pharmacology, School of Pharmacy, University College London, Brunswick Square, London WC1A 1AX, UK. a.ruiz@ucl.ac.uk.
authors.forename: Antonia
authors.initials: A
authors.lastname: Grauert
authors.forename: Dominique
authors.initials: D
authors.lastname: Engel
authors.forename: Arnaud J
authors.initials: AJ
authors.lastname: Ruiz
mesh_terms: D000818:Animals; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005029:Ethylenediamines / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
chemical_list: D020747:Calcium Channels, T-Type; D002614:Chelating Agents; D005029:Ethylenediamines; D018698:Glutamic Acid; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine